Systems and methods of rapid and autonomous detection of aerosol particles

Abstract

Disclosed are systems and methods to provide rapid and autonomous detection of analyte particles in gas and liquid samples. Disclosed are methods and devices for identifying biological aerosol analytes using MALDI-MS and chemical aerosol analytes using LDI and MALDI-MS using time-of-flight mass spectrometry (TOFMS).

What is claimed is: 
     
       1. An autonomous sample capture and analysis system for analyzing aerosol analyte particles in air, the system comprising:
 a fresh sample disk or substrate loader station configured to receive a fresh disk cartridge having one or more fresh disks; 
 a spent sample disk or substrate loader station configured to receive a spent disk cartridge; 
 an aerosol sample collection station; 
 a sample disk holder comprising a metal stub and configured to:
 removably engage with the fresh disk cartridge disposed at the fresh sample disk station to receive a fresh sample disk; 
 removably engage with the spent disk cartridge disposed at the spent sample disk station to return a spent sample disk; 
 hold a fresh sample disk or a spent sample disk; and 
 move in at least two directions (X-Y-Z) orthogonal to each other using at least one of a stepper motor and actuator using a predetermined analysis sequence; and 
 
 one or more analysis stations wherein the aerosol sample collection station is configured to produce a sample spot on a fresh disk when the sample disk holder is positioned at the collection station and wherein the operation of the system is controlled using a microcontroller configured to run a predetermined analysis sequence. 
 
     
     
       2. The system of  claim 1  wherein the system further comprises at least one of a camera station, a liquid chemical dispensing station, and a drying station. 
     
     
       3. The system of  claim 2  wherein the aerosol sample collection station is configured to produce a sample spot size of about 1 mm in diameter on the sample disk wherein the aerosol sample collection station comprises a tubing disposed in fluid communication with ambient air at one end and an impactor nozzle having a nozzle tip disposed at the other end of the tubing at a predetermined spacing above the sample disk wherein:
 the nozzle tip has a hole diameter of between about 0.35 mm and about 1 mm; and, 
 the predetermined spacing between the nozzle tip and the sample disk is between about 0.35 mm and about 1 mm. 
 
     
     
       4. The system of  claim 2  wherein the dispensing station is configured to dispense between about 0.5 μl and about 2 μl of a liquid. 
     
     
       5. The system of  claim 4  wherein the liquid comprises at least one of MALDI matrix chemical, TFA, acetonitrile, methanol, ethanol, and water. 
     
     
       6. The system of  claim 2  wherein the camera station is configured to receive at least one of a microscope camera and a digital camera. 
     
     
       7. The system of  claim 2  wherein the drying station is configured to substantially dry the sample using at least one of inductive heating, resistive heating, flow of air, and vacuum and combinations thereof. 
     
     
       8. The system of  claim 1  wherein the disks are pre-coated with a MALDI matrix chemical. 
     
     
       9. The system of  claim 1  wherein the sample disk is made of at least one of nickel and nickel alloys. 
     
     
       10. The system of  claim 1  wherein the system is configured to communicate with a remote server using at least one of wired communication and wireless communication wherein the output of the analysis station is transferred to the remote server and then to a data processing station for data processing. 
     
     
       11. The system of  claim 1  wherein the system is configured to communicate with a data processing station using at least one of wired communication and wireless communication wherein the output of the analysis station is transferred to the data processing station for processing. 
     
     
       12. The system of  claim 1  wherein the one or more analysis stations comprises at least one of a TOFMS, LDI-MS, MALDI-TOFMS, LIBS, Raman spectroscopy, fluorescence microscopy, surface enhanced RAMAN spectroscopy, scanning electron microscopy IR spectroscopy and an optical detector. 
     
     
       13. The system of  claim 1  further comprising a fluorescence sensor disposed upstream of the sample collection station to measure at least one of particle size distribution, particle count, and target analyte particle to clutter particle ratio. 
     
     
       14. A method for collecting and analyzing aerosol analyte sample particles in air using the system of  claim 13 , the method comprising:
 loading a fresh sample disk onto the sample disk holder at the fresh sample disk loader station; 
 measuring particle counts in ambient air; 
 when the particle counts exceed a predetermined threshold moving the sample disk holder having a fresh disk to the aerosol collection station where aerosol particles are impacted onto the sample disk to deposit aerosol particles onto the disk to produce a sample spot size of about 1 mm in diameter on the sample disk; 
 moving the sample disk holder to the liquid chemical dispensing station for treating the deposited aerosol particles with chemicals; 
 moving the sample disk holder to the camera station for examination using at least one of a microscope camera and imaging using a digital camera; 
 substantially drying the sample; and, 
 moving the sample disk holder to the one or more analysis stations for sample analysis. 
 
     
     
       15. The method of  claim 14  further comprising the steps of:
 analyzing the sample using TOFMS; 
 transferring the output of the TOFMS to a remote server using at least one of the wired communication and wireless communication between the autonomous sample capture and analysis system and the server; 
 generating raw spectral data unique to the aerosol analyte particles; 
 performing at least one of filtering, baseline subtraction, signal to noise ratio estimation, peak detection, and feature extraction to generate processed spectral data; and, 
 identifying the composition of the aerosol analyte particle by comparing the processed spectral data with a reference library comprising processed spectral data of several biological and chemical analytes. 
 
     
     
       16. The method of  claim 14  wherein sample disk is pre-coated with a MALDI matrix chemical. 
     
     
       17. An autonomous sample capture and analysis system for analyzing a liquid sample, the system comprising:
 a fresh sample disk or substrate loader station configured to receive a fresh disk cartridge having one or more fresh disks; 
 a spent sample disk or substrate loader station configured to receive a spent disk cartridge; 
 a liquid sample acceptance station configured to receive the liquid sample; 
 a liquid chemical dispensing station; 
 a sample disk holder comprising a metal stub and configured to:
 removably engage with the fresh disk cartridge disposed at the fresh sample disk station to receive a fresh sample disk; 
 removably engage with the spent disk cartridge disposed at the spent sample disk station to return a spent sample disk; 
 hold a fresh sample disk or a spent sample disk; and 
 move in at least two directions (X-Y-Z) orthogonal to each other using at least one of a stepper motor and actuator using a predetermined analysis sequence; and, 
 
 one or more analysis stations wherein the liquid sample acceptance station is station is configured to produce a sample spot on a fresh disk and wherein the operation of the system is controlled using a microcontroller configured to run a predetermined analysis sequence. 
 
     
     
       18. The system of  claim 17 , wherein the liquid sample acceptance station is configured to receive a liquid sample from an aerosol collection device. 
     
     
       19. The system of  claim 18  wherein the aerosol collection device comprises at least one of an impactor, a rotating impactor with continuous or intermittent rinsing, a cyclone with continuous or intermittent rinsing, a wet-walled impactor, and a liquid impinger. 
     
     
       20. The system of  claim 17  wherein the liquid sample acceptance station is configured to receive a liquid sample comprising exhaled breath. 
     
     
       21. The system of  claim 17  wherein the liquid sample acceptance station is configured to receive a liquid sample obtained from a liquid sample processing device capable of at least one of purifying, digesting, and concentrating target analytes. 
     
     
       22. A method for collecting and analyzing aerosol particles, the method comprising:
 collecting aerosol particles into a liquid; 
 subjecting the liquid sample to at least one of enzyme and hot acid treatment and generating peptides characteristic of the aerosol sample; 
 adding MALDI matrix solution to the treated sample; and, 
 drying and analyzing the sample using the system of  claim 17 . 
 
     
     
       23. An autonomous sample capture and analysis system for capturing and analyzing contaminant particles in a liquid sample, the system comprising:
 a nebulizer to produce an aerosol comprising contaminant particles in a carrier gas; 
 at least one condensation growth tube to enlarge the size of the contaminant particles in the aerosol to a predetermined average particle diameter; 
 a fresh sample disk or substrate loader station configured to receive a fresh disk cartridge having one or more fresh disks; 
 a spent sample disk or substrate loader station configured to receive a spent disk cartridge; 
 an aerosol sample collection station; 
 a liquid chemical dispensing station; 
 a camera station configured to receive at least one of a microscope camera and a digital camera; 
 a drying station to substantially dry the sample under vacuum; and, 
 a sample disk holder comprising a metal stub and configured to:
 removably engage with the fresh disk cartridge disposed at the fresh sample disk station to receive a fresh sample disk; 
 removably engage with the spent disk cartridge disposed at the spent sample disk station to return a spent sample disk; 
 hold a fresh sample disk or a spent sample disk; and 
 move in at least two directions (X-Y-Z) orthogonal to each other using at least one of a stepper motor and actuator using a predetermined analysis sequence; and, 
 
 one or more analysis stations wherein the aerosol sample collection station is configured to produce a sample spot on a fresh disk when the sample disk holder is positioned at the collection station and wherein the operation of the system is controlled using a microcontroller configured to run a predetermined analysis sequence. 
 
     
     
       24. The system of  claim 23  wherein the one or more analysis stations comprises at least one of a LDI-MS, a MALDI-TOFMS, LIBS, Raman spectroscopy, fluorescence microscopy, surface enhanced RAMAN spectroscopy, scanning electron microscopy, IR spectroscopy and an optical detector. 
     
     
       25. The system of  claim 24  wherein the disks are pre-coated with a MALDI matrix chemical. 
     
     
       26. The system of  claim 23  wherein the sample disk is made of at least one of nickel and nickel alloys. 
     
     
       27. The system of  claim 23  wherein the dispensing station is configured to dispense between about 0.5 μL and about 2 μL of a liquid. 
     
     
       28. The system of  claim 27  wherein the liquid comprises at least one of TFA, acetonitrile, methanol, ethanol, and water. 
     
     
       29. The system of  claim 23  further comprising a fluorescence sensor disposed upstream of the sample collection station to measure at least one of particle size distribution, particle count, and target analyte particle to clutter particle ratio. 
     
     
       30. The system of  claim 23  further comprising a data processing station for acquiring an processing data output from the one or more analysis stations to identify the composition of the contaminant particles. 
     
     
       31. The system of  claim 23  wherein the liquid sample comprises at least one of UPW, and chemical liquids used during semiconductor fabrication. 
     
     
       32. A method for capturing and analyzing contaminant particles in a liquid sample using the system of  claim 23 , the method comprising:
 nebulizing the liquid sample to produce an aerosol comprising contaminant particles in a carrier gas; 
 growing the size of the contaminant particles in the aerosol using at least one condensation growth tube to produce enlarged contaminant aerosol particles of predetermined average particle diameter; 
 loading a fresh sample disk onto the sample holder at the fresh sample disk loader station; 
 moving the sample holder having a fresh disk to the aerosol sample collection station where the enlarged contaminant aerosol particles are impacted onto the sample disk; 
 moving the sample holder to the liquid chemical dispensing station for treating the deposited aerosol particles with chemicals; 
 moving the sample holder to a camera station for examination using at least one of a microscope camera and imaging using a digital camera; 
 drying the sample; and, 
 moving the sample holder to an the one or more analysis stations for sample analysis. 
 
     
     
       33. The method of  claim 32  further comprising measuring at least one of particle size distribution, particle count, and target analyte particle to clutter particle ratio using a fluorescence sensor disposed upstream of the sample collection station. 
     
     
       34. The method of  claim 32  wherein the one or more analysis stations comprises at least of one of a LDI-MS, MALDI-TOFMS, LIBS, Raman spectroscopy, fluorescence microscopy, surface enhanced RAMAN spectroscopy, scanning electron microscopy, optical detector, and IR spectroscopy. 
     
     
       35. The method of  claim 32  further comprising the steps of:
 analyzing the sample using TOFMS; 
 transferring the output of the TOFMS to a remote server using at least one of the wired communication and wireless communication between the autonomous sample capture and analysis system and the server; 
 generating raw spectral data unique to the aerosol analyte particles; 
 performing at least one of filtering, baseline subtraction, signal to noise ratio estimation, peak detection, and feature extraction to generate processed spectral data; and, 
 identifying the composition of the contaminant particles by comparing the processed spectral data with a reference library comprising processed spectral data of several biological and chemical analytes. 
 
     
     
       36. The method of  claim 35  wherein the identifying step further comprises using machine learning to compare spectral data with a training data set to predict contaminant particle composition.